Single-agent pemigatinib is being compared with gemcitabine plus cisplatin in patients with unresectable and/or metastatic cholangiocarcinoma whose tumor harbor FGFR2 fusions or rearrangements in the ongoing, phase 3 FIGHT-302 trial.
Single-agent pemigatinib (Pemazyre) is being compared with gemcitabine plus cisplatin in patients with unresectable and/or metastatic cholangiocarcinoma (CCA) whose tumor harbor FGFR2 fusions or rearrangements in the ongoing, phase 3 FIGHT-302 trial (NCT03656536). The study was discussed in a poster presentation during the 2021 European Society for Medical Oncology World Congress on Gastrointestinal Cancer.1
Frontline treatment for patients with advanced CCA currently consists of gemcitabine plus cisplatin resulting in a median progression-free survival (PFS) of 8 months.2 Pemigatinib, a selective oral inhibitor of FGFR1, 2, and 3, had previously demonstrated efficacy in the phase 2 FIGHT-202 trial (NCT02924376) in patients with locally advanced or metastatic CCA with FGFR2 fusions or rearrangements.3 In that trial, investigators reported an objective response rate (ORR) of 35.5%, a median progression-free response of 6.9 months, a median duration of response (DOR) of 9.1 months, and a disease control rate (DCR) of 82%.3
In FIGHT-302, patients will be randomized 1:1 into 2 groups. In group A, patients will receive a starting dose of 13.5 mg of pemigatinib once daily on a 3-week cycle. In patients who do not achieve hyperphosphatemia, pemigatinib will be titrated up to 18 mg for cycle 2. In group B, patients will receive 1000 mg/m2 of gemcitabine plus 25 mg/m2 of cisplatin administered intravenously on days 1 and 8 of a 3-week cycle for up to 8 cycles, until disease progression or unacceptable toxicity.
To be eligible for FIGHT-302, patients must have confirmed CCA through histologic or cytologic findings; no prior treatment for advanced disease; have documented FGFR2 fusions or rearrangement; and have an ECOG performance status of 0 to 1. Exclusion criteria include previous systemic therapy, excluding adjuvant/neoadjuvant treatment completed more than 6 months before enrollment; confirmed corneal/retinal disorder; and central nervous system metastases or history of uncontrolled seizures.
Patients will be stratified geographically by 3 regions: western (North America and the European Union); Asia Pacific; and the rest of the world. Patients will be further stratified by tumor burden (locally advanced vs distant metastases).
Patients in group B may be considered for crossover if they have confirmed disease progression as determined by central review. After treatment is discontinued, patients will be followed every 12 weeks for survival status.
Patients will undergo ophthalmic examinations including visual acuity testing, slit-lamp examination, and fundoscopy once every 3 cycles, at the end of treatment, and when clinically necessary.
The primary end point is PFS and secondary end points include ORR, DOR and DCR. Exploratory end points include association of specific FGFR2 alterations with PFS, overall survival (OS), ORR, and additional biomarker measures.
During the screening period, patients will be assessed for prior/concomitant medications, adverse events, physical examinations, optical examinations, tumor imaging, ECOG performance status, ECG evaluation, and serum hematology. In cycle 1, in addition to the screening assessments, patients will also undergo quality of life assessments and pharmacokinetic study. In cycle 2, patients will undergo all previous assessments. During the follow-up period, patients will undergo evaluations for safety, disease status, and survival.